MHC molecules are proteins that sit on the surface of cells in the human body. If the cells are infected, or if they become cancerous, the MHC molecules capture and display pieces (peptides) from the proteins of the infecting organisms or the cancer cells. These displayed pieces can then be recognized by certain white blood cells called T lymphocytes. Under the right circumstances this T cell recognition can lead to an immune reaction against the infection or the cancer. Our immunology group works on the development of recombinant single chain MHC molecules in order to study their cell biology, immune function, potential use as vaccine components and to help learn how T cell populations develop that can recognize many different peptides. Class I MHC molecules on infected or cancerous cells display peptides from within these cells. Recognition of these peptides by CD8 T cells contributes to immune responses to cancers such as melanoma, and to antiviral immune responses, including resistance to HIV. In nature, the Class I molecules are formed of three components that can slowly separate. This limits the time during which an immune reaction can occur. This year, Dr. Li Lee extended her work on class I molecules by synthesizing and expressing a recombinant single chain human Class I HLA-A2.1 MHC molecule in which all three components (including the viral peptide) are covalently (tightly) attached. We are now studying the immune response to this molecule. The peptides that bind to Class II MHC molecules come from foreign proteins outside the cell that are engulfed and fragmented. These peptides are recognized by CD4 T cells that act as helper cells for antibody production. The CD4 T cells also increase or inhibit other T cell responses by secreting locally acting hormones called cytokines. During this year, Dr. Xiaojie Zhu has been able to stimulate a T cell clone and normal human blood lymphocytes with one of her recombinant single chain class II MHC molecules (HLA-DR) with a covalently attached viral peptide, showing that it is immunologically active.